Prof. Dr. Helge B. Bode

All (?) about small talk in nematode holobionts – from chemical ecology to synthetic biology

Communication within holobionts (functional units of an eukaryotic host and its microbial partners) is often mediated by low molecular-weight natural products (NPs). Our aim is to decipher the NP contribution in these interaction using methods from microbiology, biochemistry, analytical and synthetic chemistry. As a model we use entomopathogenic nematodes (Steinernema or Heterorhabditis), their bacterial symbionts (Xenorhabdus or Photorhabdus) as well as the insect prey that is infected and killed by the nematode/bacteria pair.

During the last 10 years we have identified several bacterial quorum sensing signals, inhibitors of the insect immune response, toxins, antibiotics and other factors. We have also developed tools to manipulate the production of the bacterial natural products “on demand” in order to study effects of individual compounds in this communication network and have started to elucidate the signalling network regulated by these natural products and regulating their biosynthesis. We were further able to identify conserved natural products by comparative genomics, which might play important roles in this ecological niche.

As an “applied spin-off” to this chemical ecology work, we could identify rules for the design and the manipulation of biosynthesis gene clusters encoding non-ribosomal peptide synthetases (NRPS) that allow us to efficiently modify these biosynthesis pathways and even to design completely “non-natural” peptides that can be developed into new drugs in the future.